title: Comparative evaluation of in vitro efficacy of colesevelam hydrochloride tablets.
abstract: BACKGROUND
  Colesevelam hydrochloride is used as an adjunct to diet and exercise to reduce elevated low-density lipoprotein (LDL) cholesterol in patients with primary hyperlipidemia as well as to improve glycemic control in patients with type 2 diabetes. This is likely to result in submission of abbreviated new drug applications (ANDA).
  
  
  OBJECTIVE
  This study was conducted to compare the efficacy of two tablet products of colesevelam hydrochloride based on the in vitro binding of bile acid sodium salts of glycocholic acid (GC), glycochenodeoxycholic acid (GCDA) and taurodeoxycholic acid (TDCA).
  
  
  METHODS
  Kinetic binding study was carried out with constant initial bile salt concentrations as a function of time. Equilibrium binding studies were conducted under conditions of constant incubation time and varying initial concentrations of bile acid sodium salts. The unbound concentration of bile salts was determined in the samples of these studies. Langmuir equation was utilized to calculate the binding constants k1 and k2.
  
  
  RESULTS
  The amount of the three bile salts bound to both the products reached equilibrium at 3 h. The similarity factor (f2) was 99.5 based on the binding profile of total bile salts to the test and reference colesevelam tablets as a function of time. The 90% confidence interval for the test to reference ratio of k2 values were 96.06-112.07 which is within the acceptance criteria of 80-120%.
  
  
  CONCLUSIONS
  It is concluded from the results that the test and reference tablets of colesevelam hydrochloride showed a similar in vitro binding profile and capacity to bile salts.
authors.affiliation: Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring , MD , USA and.
authors.forename: Yellela S R
authors.initials: YS
authors.lastname: Krishnaiah
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Yang
authors.forename: Srikant
authors.initials: S
authors.lastname: Bykadi
authors.forename: Vilayat A
authors.initials: VA
authors.lastname: Sayeed
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D000499:Allylamine / Q000031:analogs & derivatives* / Q000737:chemistry; D001647:Bile Acids and Salts / Q000737:chemistry; D000069472:Colesevelam Hydrochloride; D005999:Glycochenodeoxycholic Acid / Q000737:chemistry; D006000:Glycocholic Acid / Q000737:chemistry; D007700:Kinetics; D013607:Tablets / Q000737:chemistry*; D013657:Taurodeoxycholic Acid / Q000737:chemistry
chemical_list: D001647:Bile Acids and Salts; D013607:Tablets; D000499:Allylamine; D013657:Taurodeoxycholic Acid; D005999:Glycochenodeoxycholic Acid; D006000:Glycocholic Acid; D000069472:Colesevelam Hydrochloride
keywords: Affinity constant; bile salts; binding; bioequivalence; capacity constant; colesevelam hydrochloride; equilibrium; in vitro; kinetic; langmuir